Nicotine is an addictive drug that rapidly reaches the brain following inhalation of cigarette smoke. Addiction to nicotine through cigarette smoking afflicts more than 50 million people in the United States, and is responsible for approximately 350,000 deaths every year. Although the effects of nicotine on the central nervous system are likely to be the primary reason for its addictive nature, little is known about the properties of central nicotinic receptors. The experiments described here are aimed at evaluating the physiology and pharmacology of nicotinic receptors on mammalian central neurons. These studies utilize isolated and identified neurons which are maintained in culture. Electrophysiological experiments are performed using patch-clamp technology. The specific aims of this study are: 1. To examine the interaction of agonists with the central nicotinic receptor. 2. To examine the effects of antagonists. 3. To evaluate the unique characteristics of the central nicotinic receptor using a specific snake neurotoxin. 4. To investigate the properties of the receptor-associated ion pore at the single-channel level. The long term objectives of the present proposal are to characterize the functional properties of the central nicotine receptor so that pertinent information may be important in understanding and possibly alleviating nicotine addiction.